We have prepared rabbit antisera against nuclear nonhistone protein fractions from normal mouse hepatocytes and from a transplantable mouse hepatoma. These antisera give nuclear fluorescence which is specific for the immunizing tissue. Antisera to normal nuclei do not react with hepatoma nuclei and vice versa. Two-dimensional gel electrophoresis reveals significant differences between nuclear nonhistone protein fractions from normal and malignant liver tissue. Aims of present research include a) Identification of the antigens with which the above antisera react. b) Isolation of nuclear proteins that show differential expression in normal and malignant nuclei. c) Preparation of monoclonal antibodies to nuclear proteins.